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Phospholipase C-gamma1 is required for cell survival in oxidative stress by protein kinase C.
- Source :
-
The Biochemical journal [Biochem J] 2002 Apr 15; Vol. 363 (Pt 2), pp. 395-401. - Publication Year :
- 2002
-
Abstract
- Phospholipase C-gamma1 (PLC-gamma1) activation has been reported to enhance cell survival during the cellular response to oxidative stress. We studied the role of protein kinase C (PKC) pathways in mediating PLC-gamma1 survival signalling in oxidative stress by using mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcg1(-/-)) and its wild type (Plcg1(+/+)). PLC-gamma1 was activated by H(2)O(2) treatment in a dose- and time-dependent manner. Activation of PKC was also markedly increased in both cell lines treated with H(2)O(2) (1-5 mM), but with low doses (50-200 microM), PKC activation was considerably decreased in Plcg1(-/-) cells. After treatment with H(2)O(2), PKC-dependent phosphorylation of Bcl-2 and cell viability of Plcg1(-/-) cells decreased dramatically and caspase-3-like activity increased significantly compared with that of the wild-type cells. Furthermore, pretreatment of Plcg1(+/+) cells with PKC-specific inhibitor decreased levels of PKC-dependent Bcl-2 phosphorylation, enhanced caspase-3 activity and their sensitivity to H(2)O(2). On the contrary, treatment of Plcg1(-/-) cells with PKC-specific activator increased the Bcl-2 phosphorylation, decreased caspase-3 activity and improved their survival. These results suggest that PLC-gamma1 mediates survival signalling in oxidative-stress response by PKC-dependent phosphorylation of Bcl-2 and inhibition of caspase-3.
- Subjects :
- Animals
Caspase 3
Caspases metabolism
Cell Survival drug effects
Cells, Cultured
Enzyme Activation drug effects
Hydrogen Peroxide toxicity
Isoenzymes deficiency
Isoenzymes genetics
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases metabolism
Oxidative Stress drug effects
Phospholipase C gamma
Phosphorylation
Proto-Oncogene Proteins c-bcl-2 metabolism
Type C Phospholipases deficiency
Type C Phospholipases genetics
Cell Survival physiology
Isoenzymes metabolism
Oxidative Stress physiology
Protein Kinase C metabolism
Type C Phospholipases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 363
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 11931670
- Full Text :
- https://doi.org/10.1042/0264-6021:3630395